[Experimental studies of reliability of symbolic information perception from the aviation LCD panel].

Results of tachistiscopic experiments on reliability of symbol recognition on LCD panel as a function of screen definition (640 x 480, 800 x 600 and 1024 x 768 pixels), angular size of a picture element (10, 15, 20 and 30 angular min) and luminance contrast (LC) with the background (0.2 to 1.4 standard units) are presented. The obtained quantitative relations indicate significance of the above parameters for recognition reliability. Symbols with the size of 30 angular min and LC of 0.5 were recognizable irrespective of screen definition in the study. Recognition of symbols 20 and 15 angular min of size was much dependent on screen definition and LC of symbols. For symbols of size 10 angular min and LC ≥ 1.0 the recognition probability did not exceed 0.59-0.7.

[Peculiarities of pilot's perception of flight information presented on on-board liquid crystal displays].

The article deals with results of experimental studies conducted on flight testing desk and covering peculiarities of pilot's perception of flight information presented on on-board liquid crystal display in dependence on changes speed and update rate of the screen. The authors determine frequency characteristics of information update rate, that achieve acceptable quality of the flight parameters perception in accordance with the changes speed. Vigorous maneuvering with high angular velocities of changed parameters of roll and pitch causes visual distortions that are connected with poor frequency of information update rate, deteriorate piloting quality and can cause flight unsafety.

[Oligo(2'-O-Methylribonucleotides) and their derivatives: IV. Conjugates of oligo(2'-O-methylribonucleotides) with minor groove binders and intercalators: synthesis, properties and application].

Conjugates of pyrimidine triplex forming 3'-protected oligo(2'-O-methylribonucleotides) with minor groove binders (MGB) and triplex specific intercalator benzoindoloquinoline (BIQ) at 5'-terminus were synthesized. The conjugates formed stable complexes with target dsDNA by simultaneous binding both in its minor and major grooves and BIQ intercalation. The dissociation constants and thermal stability of the conjugate complexes with model dsDNA corresponding to polypurine tract (PPT) of genes nef and pol from HIV proviral genome were determined. Conjugation of oligo(2'-O-methylribonucleotides) with MGB and intercalator increased the stability of the triple complexes with dsDNA at pH 7.2 and 37 degrees C. Intercalator introduction accelerates the process of complex formation. Dose-dependent arrest of the in vitro transcription was demonstrated when a 780 b.p. DNA fragment containing the polypurine tract was transcribed under the control of T7 promoter in the presence of different concentrations of conjugates of oligo(2'-O-methylribonucleotides) containing MGB and BIQ intercalator.

[A compact microarray for sub-typing of influenza A virus].

A universal oligonucleotide hybridazation microchip 6 x 5 spot (4 x 4 mm) for influenza A virus subtyping was suggested, functioning on a principle one spot--one subtype. This microchip with additional printing quality control is a prototype of a biosensor for detection of influenza A virus and typing of 15 subtypes of hemagglutinin and 9 subtypes of neuraminidase.

[The oxidation stress, lipid metabolism and their relationship in patients with severe course of hypertension disease in aggregate with carotid stenosis].

The experimental samplings consisted of 25 patients with severe course of hypertension disease in aggregate with atherogenic carotid stenosis before and after carotid endarterectomy and 21 donors. The study was organized to analyze in lipid profile blood serum the content of malonic dialdehyde, ceruloplasmin, alpha-tocopherol, nitric oxide and angiotensin converting enzyme. The study established that in patients took place a reliably increased level of malonic dialdehyde, ceruloplasmin, alpha-tocopherol, nitric oxide and angiotensin converting enzyme. The patients with this pathology have a reliable positive correlation between the concentration of malonic dialdehydeand lipoproteids of very low density (r = 0.51), malonic dialdehyde and triglycerides (r = 0.36), malonic dialdehyde and cholesterol (r = 0.3). This data confirms the important role of peroxidation of lipids in the development of atherosclerosis. Therefore, the enhancement of oxidation stress and expressed dislipoproteidemia are established in patients with hypertension disease with carotids atherosclerosis as a background. This result testifies the pathogenic significance of these phenomena in the mechanisms of homeostasis disorders.

[The second generation universal oligonucleotide microarray for subtyping of influenza virus A].

The microchip for influenza A subtyping was developed, functioning on a principle "one spot--one subtype". Each spot contains the set of oligonucleotide probes, specific for a particular subtype of hemagglutinin, neuraminidase or matrix gene. Reliability of the proposed chip version is the same as for earlier created in our group full-size microchip for separate hemagglutinin and neuraminidase subtyping. To visualize the image, analyzed DNA can be labeled by either fluorescent dye or biotin with the further fixation in system streptavidin-gold nanoparticles and image development by silver precipitation. In the second case common version of scanner can be used for the image analysis, that essentially simplifies procedure of influenza A subtyping.

[Optimizing visual work of pilot wearing night vision glasses].

The article deals with results of experimental studies on optimizing visual work conditions of pilot in night vision glasses. Prevention of visual fatigue during work in night vision glasses was proved to be contributed mostly by the image brightness (in range of 0.7-1.8 candle/m2) adjustable by the pilot, precise individual settings of optic system in night vision glasses (by viewer's eye base) and regulation of the work duration.

[Oseltamivir resistance depends on the position 273 amino acid of neuraminidase of the type A influenza virus (H1N1), circulating in human population].

The structure of neuraminidase of the type A influenza virus (H1N1) spreading in the human population was analyzed. The obtained results indicate a significant correlation between the oseltamivir sensitivity and the nature of the amino acid localized not only to neuraminidase position 274, but also to position 273 of this protein. Phenylalanine at position 273 in neuraminidase indicates a higher propensity to influenza virus mutation H274Y, leading to the appearance of resistant strains. It is suggested that the mutation at position 273 may be one of the characteristics allowing type A influenza virus to be ascribed to a pandemic or a seasonal type.

[Microarray for diagnostics of human pathogenic influenza A viruses subtypes].

An oligonucleotide microchip was developed for diagnostics of human pathogenic Influenza A viruses subtypes. It contains discriminating probes for H1-, H2-, H3-, H5-, H7- and H9-subtypes of hemagglutinin and for N1-, N2-, and N7-subtypes of neuraminidase. The additional set of probes was used for M-gene of Influenza A viruses definition. Microchip was tested on samples pathogenic H5N1 avian influenza viruses, pandemic H1N1 swine influenza viruses and seasonal H1N1 and H3N2 influenza viruses. The microchip can be used for the analysis of both cultured strains and clinical specimens.

[Oligonucleotide microarray for subtyping of influenza virus A neuraminidase].

Microarray for influenza A neuraminidase subtyping was presented. Selection of oligoprobes proceeded in two steps. First step included selection of peptides specific for each subtype of neuraminidase. At the second step oligoprobes were calculated using found peptides structures with the subsequent additional selection of the most specific and representative probes. From 19 to 24 probes were used for determination of each subtype of neuraminidase. Microchip testing for 19 samples with the most widespread types (N1 and N2) specifies in unequivocal definition 18 of them and only one isolate has not been identified.

[Subtyping of influenza virus A hemagglutinine with hybridization microarray].

An oligonucleotide microarray for influenza A hemagglutinine subtyping was presented. The number of probes for determination of each subtype hemagglutinine (H1-H13, H15, H16, pandemic flu H1N1)varied from 13 to 28. When testing of the microarray using 40 type A influenza virus isolates the hemagglutinin subtypes were unambiguously determined for 36 specimens.

[Identification of human pathogenic variola and monkeypox viruses by real-time polymerase chain reaction].

A kit of specific oligonucleotide primers and hybridization probes has been proposed to detect orthopoxviruses (OPV) and to discriminate human pathogenic viruses, such as variola virus and monkey virus by real-time polymerase chain reaction (PCR). For real-time PCR, the following pairs of fluorophore and a fluorescence quencher were used: TAMRA-BHQ2 for genus-specific probes and FAM-BHQ1 for species-specific ones (variola virus, monkeypox virus, ectomelia virus). The specificity of this assay was tested on 38 strains of 6 OPV species and it was 100%.

[Oligonucleotide conjugates with minor groove ligands as probes for hybridization microarray chips].

A possibility of using oligonucleotide conjugates with minor groove ligands as probes for hybridization microarray chips was studied. The oligonucleotide conjugates contain a hairpin ligand (MGB) composed of two tripyrrolcarboxamide residues with an aminocaproic acid residue as a linker and bound to the oligonucleotide duplex AT tract in a site-specific manner. We used as (5'-3') probes GACAAGAp, GACAAAAp, GACAAGA-MGB, and GACAAAA-MGB. The oligonucleotides labeled with Cy3 cyanine dye, Cy3-ACTAATTTTGTC and Cy3-ACTAATCTTGTC, were used as targets. The maximal MGB effect on the fluorescence level of microarray chip spots, which caused its fourfold increase as compared with the initial unmodified duplex, was observed for the duplex containing only AT pairs in the ligand binding site. The presence of A-C and G-T mutations in the binding site (imperfect duplexes) or a C-G pair (perfect duplex) affects the change in fluorescence level to a considerably lesser degree.

[TaqMan probes based on oligonucleotide-hairpin minor groove ligand conjugates].

Hybridization of TaqMan probes derived from oligonucleotides containing fluorophores (fluorescein, FAM, or tetramethylrhodamine, (Tamra)), fluorescence quenchers (BHQ1 or BHQ2), and a conjugated hairpin ligand (MGB) composed of two tripyrrolcarboxamide residues connected through an aminobutyric acid residue were proposed for discrimination of point mutations using the real time PCR technique. Identification of point A/C substitution was shown to be highly specific for hepatitis C virus subtypes 1a and 1b with two variants of the probe (5'-3'): ATTGAGCGGGTTTAp-BHQ2-MGB for subtype 1a and FAM-ATTGAGCGGGTTGAp-BHQ1-MGB for subtype 1b. Perfect duplexes (A.T and G.C pairs) increase fluorescence in the process of amplification, whereas imperfect duplexes (A.G and T.C pairs) induce no fluorescence changes. This phenomenon enables simultaneous genotyping of hepatitis C virus subtypes 1a and 1b.

[Visual efficiency of pilot using of the night vision glasses].

Questionnaires filled out by 24 helicopter pilots using the night vision glasses (NVG) showed that minimization of the risk of visual discomfort was, first of all achieved through proper adjustment of image brightness and setting NVG time limits. The experiments enabled determination of the most favorable range of brightness (0.67-1.79 cd/m2) and rationalization of the necessity of individual adjustment depending on the light conditions and flight objectives, and NVG usage regulations to preclude visual fatigue.

[An oligonucleotide microarray for detection and discrimination of orthopoxviruses based on oligonucleotide sequences of two viral genes].

An oligonucleotide microarray for detection and identification of orthopoxviruses was developed. Genus specific and orthopoxvirus species-specific regions of the genes encoding chemokine binding and alpha/beta-interferon binding proteins were used as a target. The developed microarray allows the variola, monkeypox, cowpox, vaccinia, camel-pox and ectromelia (mousepox) viruses to be distinguished with a high degree of reliability.

[Effect of mexicor on oxidative stress in acute myocardial infarction].

Mexicor (5% solution and capsules) was used in 40 of 80 conventionally treated patients with acute myocardial infarction. The drug was given intravenously for 5 days, than intramuscularly (6-9 mg/kg) for 9 days and orally (0.1 mg t.i.d.) thereafter until discharge. Severity of oxidative stress was evaluated by K coefficient. Calculation of this coefficient required data on degree of oxidation of lipids in blood serum, serum levels of diene conjugates, malonic dialdehyde, alpha-tocopherol and ceruloplasmin. These parameters as well as activity of superoxide dismutase, glutathione peroxidase and catalase in erythrocytes were measured at admission, on days 2, 3, 7, 14 and at discharge. Mexicor treated compared with untreated (n=40) patients were characterized by diminished severity of oxidative stress at the account of lower levels of lipid peroxidation products and augmented compensatory potential of the endogenous antioxidant system.

[Interaction of HIV-1 reverse transcriptase with new minor groove ligands and their conjugates with oligonucleotides].

The influence of new non-natural regular minor groove binders (MGB), containing 2-4 imidazole, pyrrole or thiazole residues, and their conjugates with oligonucleotides, on the polymerization reaction catalyzed by HIV-1 reverse transcriptase was analyzed. Various model template-primer complexes: poly(A)-oligo(U), poly(A)-oligo(dT), poly(dA)-oligo(U), poly(dA)-oligo(dT) and activated DNA were used. The concentration of oligopeptides, giving 50% inhibition (I50) of the RT-dependent polymerization reaction, was shown to depend strongly on the structure of template-primer complexes, number and type of the heterocycle rings in the MGBs analyzed. The range of I50 for the most of the compounds studied is 7.7 x 10(-3)-1.0 x 10(-5) M. The affinity of MGB is minimal for poly(A)-oligo(U). However, some of imidazole and pyrrole-containing MGBs demonstrated unusually high affinity (I50 = 3 x 10(-9)-4 x 10(-8) M) to the above template-primer in complex with RT. The affinity of conjugates of thiazolecarboxamides with oligonucleotides complementary or partially complementary to the template, is 1-4 orders higher compared to free thiazolecarboxamides. The possible reasons of the dependence of I50 values upon the structure of the template-primer complexes, the structure of MGB, and their conjugates with oligonucleotides are discussed.

[Effect of structural factors on the stability of duplexes formed by oligonucleotide conjugates with minor groove ligands].

The effect of structural factors on the stability of duplexes formed by DNA minor groove binders conjugated with oligonucleotide mono- or diphosphoramidates of the general formula Oligo-MGBm (where Oligo is an oligonucleotide; m = 1 or 2; MGB is -L(Py)2R, L(Py)4R, -L(Im)4R, or -L(Py)4NH(CH2)3CO(Py)4R; Py is a 4-aminopyrrol-2-carboxylic acid residue, L is a gamma-aminobutyric acid or an epsilon-aminocaproic acid residue, R = OEt, NH(CH2)6NEt2, or NH(CH2)6N+Me3) was studied by the method of thermal denaturation. The mode of binder interaction with minor groove depends on the conjugate structure; it may be of the parallel head to head type for bisphosphoramidates and of the antiparallel head to tail type for monophosphoramidates of a hair-pin structure. The effects of the duplexes with parallel orientation (bisphosphoramidates, MGB is L(Py)4R, m = 2) and those of the hairpin structure with the antiparallel orientation (monophosphoramidates, MGB is L(Py)4(CH2)3CO(Py)4R, m = 1) on Tm values were close. The influence of the linker (L) and substituent (R) structures upon Tm was more pronounced for monophosphoramidate (MGB is L(Py)nR, m = 1) than for bisphosphoramidate (MGB is L(Py)nR, m = 2). No more than two oligopyrrolcarboxamide residues (either in parallel or antiparallel orientations) can be incorporated into the duplex minor groove. Moreover, it was shown by the example of monophosphoramidates (Oligo-L(Py)4R and Oligo-L(Py)4NH(CH2)3CO(Py)4R) that the addition of a second ligand capable of incorporation into the minor groove increased Tm of the corresponding duplex in comparison with the duplex formed by the starting monophosphoramidate. At the same time, the introduction of the ligand incapable of incorporating decreased the Tm value. The mode of interaction of the conjugated ligand with the oligonucleotide duplex is determined by its structure. For example, dipyrrolcarboxamide containing an ethoxy group at the ligand C-end stabilizes the duplex due to the stacking interaction with the terminal A*T pair, whereas tetrapyrrolcarboxamides stabilize the duplex by incorporation into the minor groove.